The physical effects of spinal cord injury (SCI) are most obviously observed as a loss of motor control below the level of the injury. However, less obvious but possibly more traumatic, is the immediate loss of sensory control above the injury level and the loss of visceral control, particularly the gastrointestinal (GI) tract. The vagus nere (cranial nerve X), which remains anatomically intact following a SCI, is the primary source of parasympathetic control to the stomach; yet derangements in the vago-vagal circuit suggest that signaling from the brain to the stomach and vice versa is disrupted. The motor input (efferent vagus) begins in the caudal brainstem (medulla) as neurons in the dorsal motor nucleus of the vagus (DMV) which synapse onto enteric neurons within the stomach to elicit gastric contraction or relaxation. The sensory output (afferent vagus) from the stomach back to the brainstem is via bipolar neurons in the nodose ganglia which extend from the stomach to the nucleus tractus solitarius (NTS). This sensory signal is then integrated and sent through NTS second order neurons back to the DMV to complete the vago-vagal circuit. While the pathophysiology of SCI remains to be understood, previous data has shown that diminished vagal afferent signaling from the GI tract to the NTS, in the medulla, may be responsible. In this proposal we will use an animal model of T3-SCI combined with a molecular (qRT-PCR) approach and in vivo neurophysiological and pharmacological (activity of vagus nerve and gastric motility) recordings in an aim to define the mechanisms resulting in the loss of gastric function post-SCI. Our overarching hypothesis is that following spinal cord injury, gastric inflammation initiates gastric dysmotility through TRPV1 translocation. Specifically, we will test the hypothesis that 1) following SCI, gastric inflammation increases TRPV1 synthesis and membrane trafficking within afferent vagus neurons; 2) over-expression of TRPV1 channels, after SCI, increases sensitivity of vagal afferent mechanoreceptors; 3) after SCI, TRPV1 channel activation triggers gastric dysmotility through heightened substance P release in the NTS. The data generated by the present proposal will provide valuable insight into the inflammatory mechanisms which occur post-SCI and offer therapeutic strategies to reduce such alterations, thereby improving the functional outcome of gastric dysmotility.